Project description:The Type 1 Diabetes Genetics Consortium (T1DGC) was formed to address issues of limited sample size and consistency of phenotyping that had limited genetic investigations on risk of type 1 diabetes (T1D). The T1DGC first collected affected sib pair (ASP) families from four geographic networks (Asia-Pacific, Europe, North America, United Kingdom). In addition, T1D cases and controls were ascertained from existing and de novo collections. The T1DGC assembled 2,601 T1D ASP families and 69 Parent-T1D offspring trios, T1D cases from the UK Genetic Resource Investigating Diabetes (UKGRID, N=6,670), and controls from the British 1958 Birth Cohort (B58BC, N=6,523), the UK National Blood Services collection (NBS, N=2,893) and the NIHR Cambridge Biomedical Research Centre BioResource (CBR, N=2,846). All samples included in this series have reported or self-declared European ancestry. All DNA samples were collected after approval from relevant institutional research ethics committees. Genotyping was performed using a custom Illumina Infinium high-density genotyping array, ImmunoChip (Illumina, Inc; CA) according to manufacturer's protocols. The ImmunoChip was designed to densely genotype, using 1000 Genomes and any other available disease specific resequencing data, immune-mediated disease loci identified by common variant GWAS. The ImmunoChip Consortium selected 186 distinct loci containing markers meeting genome wide significance criteria (P<5x10-8) from twelve such diseases (autoimmune thyroid disease, ankylosing spondylitis, Crohn's disease, celiac disease, IgA deficiency, multiple sclerosis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, T1D and ulcerative colitis). All 1000 Genomes Project pilot phase CEU population variants (Sept 2009 release) within 0.1cM (HapMap3 CEU) recombination blocks around each GWAS region lead marker were submitted for array design. No filtering on correlated variants (linkage disequilibrium) was applied. Additional content included regional resequencing data (submitted by several groups) as well as a small proportion of investigator-specific undisclosed content including intermediate GWAS results. After data cleaning and quality control, a total of 154,939 single nucleotide polymorphisms (SNPs) from 186 loci on ImmunoChip were scored. Case-control and family data were analyzed independently and combined by meta-analysis.

Project description:Cases with Type 1 Diabetes (T1D) in the UK, were part of the Wellcome Trust Case Control Consortium (WTCCC) - <a href="http://www.wtccc.org.uk" target="_blank">http://www.wtccc.org.uk</a> - that first reported in 2007: Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661-678. [PubMed: <a href="http://www.ncbi.nlm.nih.gov/pubmed/17554300" target="_blank">17554300</a>] In this genome-wide association study (GWAS), funded by the NIH and JDRF, and sponsored by the Type 1 Diabetes Genetics Consortium (T1DGC), we were able to extend the case and control groups used in the WTCCC, with the intention of performing a well-powered meta-analysis. The study is written up as: Barrett, J.C., Clayton, D.G., Concannon, P., Akolkar, B., Cooper, J.D., Erlich, H.A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Plagnol, V., Pociot, F., Schuilenburg, H., Smyth, D.J., Stevens, H., Todd, J.A., Walker, N.M., Rich, S.S. and The Type 1 Diabetes Genetics Consortium Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19430480" target="_blank">19430480</a>. Resources - data: * Case data from this study is deposited here (i.e. in dbGaP) * Control data from this experiment - with subjects from the 1958 British Birth Cohort - is deposited with the European Genotype Archive (EGA): <a href="http://www.ebi.ac.uk/ega/" target="_blank">http://www.ebi.ac.uk/ega/</a> from where the WTCCC data is also available. * A complete description of how to request all components of the meta-analysis is available at: <a href="http://www.t1dbase.org/page/PosterView/display/poster_id/324" target="_blank">http://www.t1dbase.org/page/PosterView/display/poster_id/324</a> * Additional genetic data on the same case subjects, including some HLA types, are available from the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory (JDRF/WT-DIL): <a href="http://www-gene.cimr.cam.ac.uk/todd/" target="_blank">http://www-gene.cimr.cam.ac.uk/todd/</a> Resources - samples: Case and control DNA samples are also available: * Case DNA samples are available from the JDRF/WT-DIL, as above, and will be available from the NIDDK Genetics Repository at Rutgers: <a href="https://www.niddkrepository.org" target="_blank">https://www.niddkrepository.org</a> * Control DNA samples are available from the 1958 British Birth Cohort (aka National Child Development Study): <a href="http://www.cls.ioe.ac.uk/studies.asp?section=000100020003" target="_blank">http://www.cls.ioe.ac.uk/studies.asp?section=000100020003</a> Use restrictions: There are access limitations to both data and samples, in order to keep their use in line with subjects' consent.

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Type 1 Diabetes Genetics Consortium (T1DGC) ImmunoChip Study

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